The present invention relates generally to the field of mass spectrometry and its application to proteomics and system biology. Specifically, the invention relates to a combination of microfluidics systems with NEMS to form a compact mass spectrometer which can be used for sample analysis, such as for the analysis of biological samples, or the analysis of environmental pollutants.
Mass spectroscopy (MS) is one of the most important tools in the molecular biologist's arsenal for quantitative genomics and proteomics. Although MS-based proteomics is still an emerging technology where revolutionary change is possible, several concepts previously proposed are now under development or have been developed and have the potential to alter the landscape of current MS-based proteomic technologies. One of these is the analysis of intact proteins. The currency of essentially all MS-based identifications is peptides. The convergence of mass spectrometers with large mass ranges, extremely high mass accuracy and resolution, and ionization/fragmentation methods compatible with large proteins has catalyzed the emergence of whole-protein proteomics.
Recent successes illustrate the role of mass spectrometry-based proteomics as an indispensable tool for molecular and cellular biology and for the emerging field of systems biology. The ability of mass spectrometry to identify and, increasingly, to precisely quantify thousands of proteins from complex samples can be expected to impact broadly on biology and medicine. See R. Aebersold, M. Mann, Nature 422, 198 (2003). Presently there is no other technology that can rival the speed, sensitivity, and exact molecular characterization of proteins that MS based methods allow. See L. R. B. Jasminka Godovac-Zimmermann, Mass Spectrometry Reviews 20, 1 (2001). Realistically, however, the sensitivity should be down to the level of about 10 copies per cell on the assumption that if there are 10 copies in a cell, they're actually doing something of note. Progress in systems biology requires the development of protocols that enable studies with resolution at the level of the individual cell with very high throughput. Achieving this, of course, will require protocols having the capability of analyzing few-to-a single molecule in a cell so that the rarest of biomolecular species are identified, e.g., transcription factors and signaling molecules, which exert control over critical “nodes” within the bio-information cascade.
With single-cell resolution it will ultimately become possible to routinely stratify the fine details of biological sub-processes within populations, resolving individual pathways and reactions that are hidden from standard cell-culture-scale ensemble averages.